N⁶‐Methyladenosine (m⁶A) is the most common modification of messenger RNA (mRNA) in mammals. It critically influences RNA metabolism and plays an essential role in virtually all types of bioprocesses including gene expression, tissue development, self‐renewal and differentiation of stem cells, stress response and circadian clock control. It plays a crucial role in carcinogenesis and could be used as a prognostic and a diagnostic tool and as a target for new anticancer therapies. m⁶A modification is dynamically and reversibly regulated by three types of proteins. Methyltransferases, so‐called “writers” add a methyl group to the adenosine, which can be removed by demethylases, also called “erasers.” m⁶A‐specific RNA‐binding proteins, from here on referred to as “readers,” preferentially bind to the m⁶A site and mediate biological functions, such as translation, splicing or decay of RNA. In this study, we examined the expression of the six m⁶A readers HNRNPA2B1, HNRNPC, YTHDC1 and YTHDF1‐3 in clear cell renal carcinoma (ccRCC). We show that on mRNA level the expression of all six m⁶A readers is significantly downregulated compared to normal renal tissue and on protein level five out of six readers are dysregulated. Lower levels of some m⁶A readers are correlated with advanced stage and grade as well as associated with a shorter overall, progression‐free and cancer‐specific survival. In summary, we could show that m⁶A readers are dysregulated in ccRCC and might therefore act as a tumor marker, could give further information on the individual prognosis and be a target of innovative cancer therapy.

中文翻译：

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N6-甲基腺苷（m6A）阅读器在肾细胞癌中失调

N ^{6 ‐}甲基腺苷 (m ⁶ A) 是哺乳动物中最常见的信使 RNA (mRNA) 修饰。它严重影响 RNA 代谢，并在几乎所有类型的生物过程中发挥重要作用，包括基因表达、组织发育、自我更新和干细胞分化、应激反应和生物钟控制。它在致癌作用中起着至关重要的作用，可用作预后和诊断工具以及新抗癌疗法的靶点。m ⁶修饰受三种类型的蛋白质动态和可逆调节。甲基转移酶，即所谓的“写入者”，在腺苷上添加一个甲基，可以通过去甲基化酶（也称为“橡皮擦”）去除。米⁶A 特异性 RNA 结合蛋白，以下称为“阅读器”，优先结合 m ⁶ A 位点并介导生物学功能，例如 RNA 的翻译、剪接或衰变。在本研究中，我们检测了 6 个 m ⁶ A 阅读器 HNRNPA2B1、HNRNPC、YTHDC1 和 YTHDF1-3 在肾透明细胞癌 (ccRCC) 中的表达。我们表明，在 mRNA 水平上，与正常肾组织相比，所有六个 m ⁶ A 阅读器的表达均显着下调，而在蛋白质水平上，六个阅读器中有五个是失调的。某些 m ⁶ A 阅读器水平较低与晚期和分级相关，并与较短的总体、无进展和癌症特异性生存期相关。总之，我们可以证明 m ⁶阅读器在 ccRCC 中失调，因此可能充当肿瘤标志物，可以提供有关个体预后的进一步信息，并成为创新癌症治疗的目标。